心脏特异表达LMNA^E82K转基因小鼠的建立

目的建立心脏特异表达LMNAE82K转基因小鼠,为研究LMNAE82K与心肌病发病机制的关系提供工具动物。方法把LMNAE82K基因插入α-MHC启动子下游,构建转基因表达载体,显微注射法建立C57BL/6JLMNAE82K转基因小鼠,PCR鉴定转基因小鼠的基因型,采用Western Blot鉴定LMNAE82K在心脏组织中的表达,H＆E染色和超声检测转基因小鼠心脏的病理改变。结果建立了2个心脏组织特异表达LMNAE82K的转基因小鼠品系。超声检查显示转基因小鼠心室壁变薄,收缩期容积和舒张期容积增加,射血分数及短轴缩短率降低。结论LMNAE82K转基因小鼠具有LMNAE82K引起的家族性扩心病有类似的病理变化,为研究LMNAE82K与心肌病发病机制的关系的研究提供了有价值的疾病动物模型。

Establishment of Heart-specific LMNA^E82K Expression Transgenic Mice

Objective To generate the heart-specific LMNA E82K expression transgenic mice and an animal model for the study of its effects on cardiomyopathy.Methods The transgenic vector was constructed by inserting the human LMNA E82K gene into the down stream of α-MHC promoter.The transgenic mice were created by the method of microinjection.The genotype of transgenic line was identified by PCR and the expression level of the gene was determined by Western Blot.The pathologic changes were analyzed with echocardiography.Results Two lines of C57BL/6J transgenic mice with high level of LMNA E82K expression were established.The heart of LMNA E82K transgenic mice showed thinner ventricular wall and enlarged ventricular chamber compared with that of the wild type.The ejection fraction（EF%） and fractionl shortening（FS%） of the transgenic mice were decreased than those of the wild type mice.Conclusions The expression of mutant LMNA E82K gene in heart caused thin ventricular wall and ventricular chamber enlargement,which was similar with human family dilated cardiomyopathy caused by LMNA E82K mutation.The transgenic mouse could be an useful animal model for the research of LMNA E82K caused DCM.